We recently proposed that kidney kininogenase may contribute to water and salt metabolism by acting as a natriuretic factor, since we found a significant correlation between kallikrein and sodium excretion in rats having varying sodium intake and in animals having severe hypertension. We also found that blood kinins and urinary kallikrein in dogs were increased immediately after acute salt loading. Contradictory results, however, have been recently reported by Margolius et al. It should be noted, though, that the methodology of the kallikrein assay has not been uniform. To resolve these discrepancies the development of more specific methods are needed. We therefore developed a radioimmunoassay for the measurement of the kallikrein-kinin system. Using this method, we intend to study the kallikrein-kinin system as it relates to water and sodium metabolism, renal function, plasma renin, and blood pressure in animals in the following experimental situations: a) acute sodium and/or water loading; b) variable sodium intake but constant water intake and vice versa in chronic experiments; c) different developmental stages of renal hypertension produced by clipping one kidney and leaving the contralateral untouched or removed; d) removal of 70% of the renal mass; and e) secondary aldosteronism produced by constricting the inferior vena cava. Knowledge of the renal kallikrein-kinin system and its relation to sodium and water metabolism and renal function is important since it could lead to a better understanding of such diseases as hypertension, congestive heart failure, and renal edema.